Regio- and stereoselective ring opening of enantiomerically enriched 2-aryl oxetanes and 2-aryl azetidines with aryl borates.
The regioselective ring opening of 2-aryl-substituted four-membered heterocyclic rings with phenols, including catechol, was achieved by the use of aryl borates in mild and neutral reaction conditions without the aid of any transition metal catalysts. While N-alkyl azetidines were found not to be reactive, optically active N-tosyl azetidines gave the corresponding beta-aryloxy amines in a racemic form, thus indicating the considerable carbocationic character of the transition state. The introduction of a hydroxyl group in the azetidine ring (i.e., an azetidinol), able to anchor the aryl borate and to direct the subsequent nucleophilic delivery, was shown to determine the ring-opening process with predominant inversion of configuration. When enantiomerically enriched 2-aryl oxetanes were used, the reduced extent of racemization observed (up to 93:7 er) was rationalized by an intramolecular delivery through a six-membered transition state, giving beta-aryloxy alcohols with a predominant retention of configuration (i.e., a syn-stereoselective ring opening). The aryloxy alcohols obtained, endowed with suitable functionalities, can be cyclized to give access to enantiomerically enriched 2-aryl-1,5-benzodioxepins.
Bertolini
Ferruccio
F
Dipartimento di Chimica Bioorganica e Biofarmacia, Università di Pisa, Via Bonanno 33, 56126 Pisa, Italy.
Crotti
Stefano
S
Di Bussolo
Valeria
V
Macchia
Franco
F
Pineschi
Mauro
M
D001384:Azetidines / Q000737:chemistry*; D001584:Benzoxepins / Q000737:chemistry; D001881:Borates / Q000737:chemistry*; D004988:Ethers, Cyclic / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity
D001384:Azetidines; D001584:Benzoxepins; D001881:Borates; D004988:Ethers, Cyclic; D010636:Phenols; C082735:azetidine; C005287:oxetane